Status quo: Immuntherapie in der Uroonkologie

Das Jahr 2016 markiert das Jahr der Immunonkologie bei urologischen Tumoren. Es wurde als erster Vertreter der Immuncheckpoint-Inhibitoren bei uroonkologischen Tumoren der PD-1-Antikörper Nivolumab beim fortgeschrittenen Nierenzellkarzinom in der zweiten Therapielinie (nach „Vortherapie“) zugelassen. Grundlage für die Zulassung von Nivolumab waren Daten der Phase-III-Studie CheckMate-025, in der Nivolumab im Vergleich zu Everolimus bei Patienten mit fortgeschrittenem klarzelligen Nierenzellkarzinom (RCC) nach Vortherapie mit einem Angiogeneseinhibitor untersucht wurde. Für den PD-1-Antikörper wurden eine höhere Remissionsrate (25 % vs. 5 %) und eine Verlängerung des Gesamtüberlebens um 5,4 Monate im Vergleich zu Everolimus analysiert.

In den USA wurde zudem der Anti-PD-1-Antikörper Atezolizumab beim metastasierten Urothelkarzinom nach platinbasierter Chemotherapie zugelassen. Ausschlaggebend dafür waren Phase-II-Daten der IMvigor-210-Studie, die eine Gesamtansprechrate von 15 % belegt. Das mediane Gesamtüberleben (mOS) betrug 7,9 Monate in der Gesamtpopulation.

Die Substanzgruppe der Immuncheckpoint-Inhibitoren zeichnet sich durch geringe Nebenwirkungen aus. Derzeit werden in zahlreichen Phase-III-Studien Immuncheckpoint-Inhibitoren geprüft, um bisherige Erstlinien-Standardtherapien bei metastasierten urologischen Tumoren abzulösen.

The year 2016 marks the year of the immune therapy in urological cancers. The anti-PD-1 antibody Nivolumab has been approved as the first immune checkpoint inhibitor for the treatment of urological cancer, namely for advanced, previously treated renal cell carcinoma. This approval was based on CheckMate-025, a phase-III-trail analysing Nivolumab compared with Everolimus in patients previously treated with angiogenetic drugs. Nivolumab has achieved a higher rate of remission (25 vs. 5%) and a 5,4-month increase in overall survival (25,0 vs. 19,6 months).

Moreover in the US Atezolizomab has been approved by the FDA for metastatic urothelial carcinoma after platinum-based chemotherapy. Data of a phase-II-trail (IMvigor 210) demonstrated an overall response rate of 15 %. Median survival was 7.9 months for all patients with advanced urothelial cancer after platinum-based chemotherapy treated with Atezulizumab.

The side-effects resulting from immune checkpoint therapy are comparatively low. Immune checkpoint inhibitors are beeing tested in a large number of clinical trails. It is expected that this new class of drugs have the potential to replace current first-line treatment options for metastatic urological tumors such as renal cell carcinoma or urothelial carcinoma.

Key words

Immune therapy - renal cell carcinoma - urothelial carcinoma - PDL1

• Literatur

• 1 Topalian SL, Drake CG, Pardoll DM. Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol 2012; 24: 207-212
• 2 Powles T et al MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 2014; 515: 558-562
• 3 Bellmunt J, Théodore C, Demkov T et al Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol 2009; 27: 4454-4461
• 4 Balar AV et al Atezolizumab (atezo) as first-line (1L) therapy in cisplatin-ineligible locally advanced/metastatic urothelial carcinoma (mUC): Primary analysis of IMvigor210 cohort 1. J Clin Oncol. 2016 34. (suppl; abstr LBA4500); oral presentation
• 5 Rosenberg JE, Hoffman-Censits J, Powles T et al Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 2016; 387: 1909-1920
• 6 Grimm MO. Immunooncology in Urologic Cancers: Current Status. Aktuelle Urol 2016; 47: 374-377
• 7 De Santis M, Bellmunt J, Mead G et al Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer “unfit” for cisplatin-based chemotherapy: phase II--results of EORTC study 30986. J Clin Oncol 2009; 27: 5634-5639
• 8 Massard C et al Safety and efficacy of durvalumab (MEDI4736), a PD-L1 antibody, in urothelial bladder cancer. ASCO. 2016 Abstr. 4502
• 9 Galsky MD et al ESMO 2016, Proffered Paper Session - Genitourinary Tumours. Non-Prostate, Abstract No. LBA31_PR
• 10 Balar AV et al ESMO 2016, Proffered Paper Session − Genitourinary Tumours. Non-Prostate; Abstract No. LBA32_PR
• 11 Robert-Koch-Institut: Krebs in Deutschland 2009/2010. 9. Berlin: 2013
• 12 Kruck S, Bedke J, Kuczyk MA, Merseburger AS. Second-line systemic therapy for the treatment of metastatic renal cell cancer. Expert Rev Anticancer Ther 2012; 12: 777-785
• 13 Choueiri TK, Escudier B, Powles T et al Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol 2016; 17: 917-927
• 14 Motzer RJ, Hutson TE, Glen H et al Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol 2015; 16: 1473-1482
• 15 Motzer RJ, Escudier B, McDermott DF et al Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med 2015; 373: 1803-1813
• 16 McDermott DF, Motzer RJ, Atkins MB et al Long-term overall survival (OS) with nivolumab in previously treated patients with advanced renal cell carcinoma (aRCC) from phase I and II studies. J Clin Oncol. 2016 34. (suppl; abstr 4507)
• 17 McDermott DF et al Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab. J Clin Oncol 2015; 33: 2013-2020
• 18 Motzer RJ, Rini BI, McDermott DF et al Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial. J Clin Oncol 2015; 33: 1430-1437
• 19 Zaretsky JM, Garcia-Diaz A, Shin DS et al Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma. N Engl J Med 2016; 375: 819-829
• 20 Bochner BH. Re: Atezolizumab in Patients with Locally Advanced and Metastatic Urothelial Carcinoma who have Progressed Following Treatment with Platinum-based Chemotherapy: A Single-arm, Multicenter, Phase 2 Trial. Eur Urol. 2016 pii: S0302-2838(16)30715-1 [Epub ahead of print]